An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation

Traub, Stephanie and Nikonova, Alexandra and Carruthers, Alan and Dunmore, Rebecca and Vousden, Katherine A. and Gogsadze, Leila and Hao, Weidong and Zhu, Qing and Bernard, Katie and Zhu, Jie and Dymond, Michael and McLean, Gary R. and Walton, Ross P. and Glanville, Nicholas and Humbles, Alison and Khaitov, Musa and Wells, Ted and Kolbeck, Roland and Leishman, Andrew J. and Sleeman, Matthew A. and Bartlett, Nathan W. and Johnston, Sebastian L. (2013) An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. PLoS pathogens, 9 (8). pp. 1-14. ISSN 1553-7374

[img]
Preview
Text
PLoSPath_2013.pdf - Published Version

Download (1MB) | Preview

Abstract

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo.

Item Type: Article
Uncontrolled Keywords: human rhinoviruses (HRV), human intercellular adhesion molecule-1 (ICAM-1)
Subjects: 600 Technology > 610 Medicine & health
Department: School of Human Sciences
Depositing User: Gary Mclean
Date Deposited: 03 Aug 2015 09:23
Last Modified: 18 Aug 2015 10:35
URI: http://repository.londonmet.ac.uk/id/eprint/730

Actions (login required)

View Item View Item